Hepatits & Vaccines Flashcards
Viral Hepatitis - overview
Hepatits: inflammation of the liver
Primary & Secondary viral agents
Primary: A, B, C, D, E & G (95% of cases)
Secondary: EBV, CMV, Herpes virus
Acute & chronic forms
Hepatitis A
Underdeveloped/developing countries
Fecal-oral transmission during early phase of accute illness (shed in feces up to 4 weeks after infection)
Incidence not increased in health care workers or dialysis
Hepatits B
Decreasing dramatically in last 15 years in US
Transmission through blood transfusion, needlestick accidents, contaminated needles.
Can be transmitted in the absence of obvious parenteral exposure
It’s a bird, it’s a plane, it’s SUPER INFECTION (with Hep D)
Hepatits C
Prevalent in US & Western Europe
Major cause of chronic hepatits worldwide
Transmission primarily by percutaneous contact with infected blood/blood products
Healthcare workers need to take care to avoid needlestick injuries
Hepatits D
Severe & rapidly progressive liver disease
No proven effective therapy :(
Hepatits E
Fecal-oral tranmission, associated with poor sanitation
Not associated with chonic liver disease
Most infections self-limited, mild.
10-20% of HEV infections in pregnane wormen result in fulminant hepitits (especially in 3rd trimester)
Hepatitis G
Blood borne agent.
Transmission via blood transfusion, IV drug users.
Common coinfection HCV. 900-2000 infections per year, most asymptomatic.
Chronic disease rare/may not occur at all.
Goal of Vaccination
To produce artificially acquired, active immunity against a specific disease
Vaccination against contagious infectious diseases worldwide has been a positive influence
Promotes herd immunity—majority of population has immunity to specific microbe
What is a Vaccine
Purpose is to stimulate active immunity and create an immune memory so exposure of an active disease microorganism will stimulate the immune system to fight the disease
Traditional vaccine—biological suspension of weakened or killed entire pathogens so they cannot cause disease
Vaccine History
Vaccination saves approx. 3 million people a year
History actually begins as early as 1000 BCE China with smallpox
Between the 1940s-1980s there was reduced antivaccination movement
-Boom in scientific discovery and production
-Desire to protect children
-Increase in birth rate among more educated and affluent parent who accepted use of vaccines
1970s—more vaccines added to the schedule—antivax movement increased
1990s—suspicion of vaccines causing autism
Inactivated Vaccines
Manufactured by killing an infectious microbe with chemicals, heat, or radiations
More stable and safer than live vaccines (can’t mutate back to disease causing state)
Don’t require refrigeration and can be stored and shipped in freeze-dried form
Stimulate a weaker immune response than live viruses
Innactivated Whole Virus Vaccines
Polio, influenza, hepatitis A, rabies, Japanese encephalitis
Innactivated Whole Bacteria Vaccines
Pertussis, cholera, typhoid
Live, Attenuated Vaccines
Due to advances in tissue culture techniques
Created by modifying a disease-producing “wild” virus or bacterium that had been weakened in the lab to prevent the organism from causing disease
Closest thing to exposure to natural infection
Provoke strong cellular and antibody immune response, often life-long immunity
More difficult to create for complex pathogens like bacteria and parasites
Live, Attenuated Viral Vaccines
MMR, rotavirus, smallpox, varicella, yellow fever, zoster, polio (oral), influenza (nasal)
Live, Attenuated Bacterial Vaccines
Bacillus Calmette-Guerin (BCG) (mycobacterium)
oral typhoid
Nucleic Acid Vaccines
Gene-based vaccines simply encode a chosen viral protein in DNA or mRNA
Able to induce both specific humoral and cellular immune responses
Allow a high degree of adaptability to encode for any antigen
DNA Vaccines
Dispense with both the whole organism and its components
Use the genes that code for antigens
Evokes a strong antibody response to the free-floating antigen secreted by cell
Stimulates a strong cellular response against microbial antigens displayed on cell surfaces
RNA VAccines - background info
Represent the most recently developed technology
Vaccines based on mRNA are an intermediary between DNA and protein
mRNA molecule is composed of nucleotides linked in a unique order to convey genetic information for the cells to produce the proteins or antigens encoded by mRNA
2 major types of RNA vaccines
Non-replicating mRNA
-Simply construct, small size of RNA, absence of additional encoded proteins
Self-amplifying mRNA
-High levels of antigen expression—genetic information amplified many times
Virus-Like Particle (VLP) Vaccines
Multiprotein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome
Prompt an immune response similar to natural virus
Non-infectious—no genetic material
Subunit Vaccines & Carriers
Don’t contain live components of the pathogen
Contain only antigenic parts of the pathogen
Adjuvants are critical to the protective effects—antigens alone are not sufficient to induce adequate long-term immunity
Recombinant Protein Vaccine
A small piece of DNA is taken from the virus or bacteria and inserted into manufacturing cells (bacterial or yeast cells), the cells then are able to produce the surface proteins
Examples: Hepatitis B, Influenza, Acellular pertussis, HPV
Polysaccharide & Conjugate Vaccines
Polysaccharide from a pathogen is attached or “conjugated” to a protein antigen
Can improve outcomes
Conjugation changes the immune response from T cell independent to T cell dependent—produces increased immunogenicity in infants
Examples: Meningococcal, Pneumococcal, Salmonella typhi
Replicating and Nonreplicating Viral Vector-Based Vaccines
Combine many of the positive qualities of DNA vaccines and live, attenuated vaccines
Vector—using virus or bacterium as a carrier
Uses either live replicating or non-replicating vectors
Common vectors: adenovirus, measles virus, vesicular stomatitis virus
Recombinant vector vaccines are live replicating viruses engineered to carry extra genes derived from a pathogen—these extra genes produce proteins to generate immunity
What is the FDA’s Center for Biologics Evaluation & Research responsible for regulating?
Vaccines in the US
Steps of Vaccine Development
- Identify and Sequence the Virus
- Determine the Target
- Conduct Preclinical Trials
- Initial Human Trials—4 phases
- Obtain Regulatory Approval
- Establish Manufacturing and Distribution
Host Response to Vaccination
Its not clear why the length of acquired protection varies with different vaccines
Booster can be described as a “reminder” to the immune system
Depending on the vaccine, some immunizations must be repeated
A patient’s immune system responds to a vaccine in various ways
B cells and cytotoxic T cell are responsible for regulation on an immune response
Types of Vaccine Administration
Injection, orally, nasal spray
Sites of Vaccine Administration - Intramuscular injection
most common; injected into the muscle mass
Sites of Vaccine Administration - Subcutaneous (SC)
injected into the subcutaneous layer above the muscle and below the skin
Sites of Vaccine Administration - Intradermal (ID)
administers the vaccine in the topmost layer of skin
Bascillus Calmette-Guerin (BCG) is the only to use this—reduces the risk of neurovascular injury
Sites of Vaccine Administration - Intranasal Spray
offers a needle-free approach through the nasal mucosa
HIV/AIDS Vaccine Development - 3 types being researched
Preventative or prophylactic vaccines (to protect individuals from HIV infection)
Therapeutic vaccines (to prevent HIV-infected patients from progressing to AIDS)
Perinatal vaccines (to prevent HIV-infected pregnant women to prevent transmission of HIV to the fetus)
HIV/AIDS Vaccine Development - Challenges
High rate of viral mutation and recombination
No clearly defined natural immunity to HIV
HIV infects cells that are critical to the immune body defenses; also, it is transmitted as a free virus and within infected cells
HIV/AIDS Vaccine Development - Additional Problems
Lack of knowledge related to the critical components on the body’s response to HIV infection
High risk of using the entire weakened or inactive HIV in a vaccine
Extensive rate of viral mutation as HIV replicates. Strains vary by as much as 35%
Protective effect may last only a short time
Vaccinated persons could become more susceptible to HIV
No research studies have successfully demonstrated which immune responses correlate with protection from HIV infection
Cancer Vaccines - Background
Classified as “Biological-response modifiers”
Two types: Preventative/prophylactic (2) or Therapeutic (1)
Cancer treatment vaccines are designed to work by activating B cells and killer T cell and directing them to recognize and act against specific types of cancer
Cancer cells carry self- and cancer-associated antigens
The cancer associated antigens mark the cancer cells as abnormal (non-self) and can cause B cells and killer T cells to mount an attack against them
HPV Vaccine
Prophylactic
Cervarix
-Bivalent vaccine made from virus-like particles with proteins from HPV types 16 and 18; may provide partial protection against other strains
-For girls and women aged 9-25 years
Gardasil
-Quadrivalent vaccine
-Can prevent cervical cancer and vaginal and vulvar precancers caused by HPV-16 and HPV-18
-Also protects against HPV-6 and HPV-11 which are responsible for 90% of all cases of genital warts in males and females but doesn’t cause cancer
Cancer Treatment Vaccine
Intended to delay or stop the growth of cancer, to cause shrinkage of tumors, to prevent cancer from coming back, or to eliminate cancer cells that have not been destroyed by other treatments
Made using antigens from malignant cells or modified versions of them
Much more difficult to develop a cancer treatment vaccine than a preventative vaccine
To be effective a cancer vaccine must:
-Stimulate specific responses against the correct target
-Be powerful enough to over come the barriers that malignant cells use to protect themselves from attack by B cells and killer T cells
Novel Leukemia Vaccine Therapy - Does it exist?
No
As of early 2020, no FDA approved vaccines for prevention of leukemia in humans
Vaccines & Biodefense
Goal of FDA is to foster the development of vaccines that could be needed for potential products of bioterrorism
Smallpox & Anthrax main two concerns
Vaccine Safety Issues
Controversial public health issue—no vaccine is totally effective or 100% safe
The same components that make them effective, also may cause serious side effects—may not be possible to develop safer versions without losing essential function
FDA Approved vaccines must meet what requirements?
Produce protective immunity with only minimal side effects
Be immunogenic enough to produce a strong and measurable immune response
Be stable during shelf life, with potency remaining at a proper level
Vaccine Side Effects/Adverse Events
Adverse event: possible side effect resulting from a vaccination
Most are mild: soreness, swelling or redness at the injection site
Some are associated with fever, rash, achiness
Serious side effects are rare but can include seizure or life-threatening allergic reaction
Range of possible side effects—each year due to chance alone many babies will experience a medical event in close proximity to a vaccination
Monitoring Adverse Vaccine Events
1986 Congress enacted the National Childhood Vaccine Injury Act (NCVIA)—established a no-fault compensation system for children who were harmed by adverse events after the administration of a vaccine if there was evidence that the vaccine actually caused the problem
Monitoring programs are systems to monitor and analyze reported adverse event and to determine whether they are likely related to vaccinations
-Vaccine Adverse Events Reporting System (VAERS)
-Rapid Cycle Analysis—used mainly for new vaccines
Vaccines against bacterial diseases
Cholera
Group A Streptococcus-in development
Lyme Disease
Pertussis
Tuberculosis-in development
Vaccines Against Viral Diseases
Coronaviruses –in development
Dengue Fever
Ebola
Hepatitis
HIV - in development
Influenza
Respiratory Syncytial Viru (RSV)
Smallpox
West Nile Virus
Zika Virus
Review significant epidemics/pandemics etc at end of slideshow
if you’re so inclined
